Phencyclidine is a hallucinogenic drug of abuse, whose mechanism of action in the brain is largely unknown. This project seeks to characterize its effects on particular neuronal pathways in animals by the use of electrophysiological techniques. To permit the study of individual, identified neuronal circuits, intraocular transplants of specific regions of the brain will be used. Thus, interactions with neuronal circuits containing norepinephrine, dopamine, acetylcholine, serotonin, and other neurotransmitters will be studied in isolation. To permit the correlation of neuronal effects with changes in behavior, unanesthetized animals with chronically implanted electrodes will also be used. Changes in the effects of phencyclidine after chronic administration and the development of tolerance will be examined. Changes in activity of particular neuronal circuits during self administration will also be measured. Results will be compared with those obtained with amphetamine, whose mechansim of action is somewhat better understood. The interaction of these drugs with possible therapeutic agents used for the treatment of phencyclidine and amphetamine psychoses, such as lithium carbonate and neuroleptics, will also be studied.